PMID- 35771717 OWN - NLM STAT- MEDLINE DCOM- 20221011 LR - 20221231 IS - 1098-2264 (Electronic) IS - 1045-2257 (Print) IS - 1045-2257 (Linking) VI - 61 IP - 12 DP - 2022 Dec TI - Characterization of unusual iAMP21 B-lymphoblastic leukemia (iAMP21-ALL) from the Mayo Clinic and Children's Oncology Group. PG - 710-719 LID - 10.1002/gcc.23084 [doi] AB - Acute lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21-ALL) represents a recurrent high-risk cytogenetic abnormality and accurate identification is critical for appropriate clinical management. Identification of iAMP21-ALL has historically relied on fluorescence in situ hybridization (FISH) using a RUNX1 probe. Current classification requires >/= five copies of RUNX1 per cell and >/= three additional copies of RUNX1 on a single abnormal iAMP21-chromosome. We sought to evaluate the performance of the RUNX1 probe in the identification of iAMP21-ALL. This study was a retrospective evaluation of iAMP21-ALL in the Mayo Clinic and Children's Oncology Group cohorts. Of 207 cases of iAMP21-ALL, 188 (91%) were classified as "typical" iAMP21-ALL, while 19 (9%) cases were classified as "unusual" iAMP21-ALL. The "unusual" iAMP21 cases did not meet the current definition of iAMP21 by FISH but were confirmed to have iAMP21 by chromosomal microarray. Half of the "unusual" iAMP21-ALL cases had less than five RUNX1 signals, while the remainder had >/= five RUNX1 signals with some located apart from the abnormal iAMP21-chromosome. Nine percent of iAMP21-ALL cases fail to meet the FISH definition of iAMP21-ALL demonstrating that laboratories are at risk of misidentification of iAMP21-ALL when relying only on the RUNX1 FISH probe. Incorporation of chromosomal microarray testing circumvents these risks. CI - (c) 2022 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC. FAU - Koleilat, Alaa AU - Koleilat A AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Smadbeck, James B AU - Smadbeck JB AD - Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA. FAU - Zepeda-Mendoza, Cinthya J AU - Zepeda-Mendoza CJ AD - ARUP Laboratories, Salt Lake City, Utah, USA. FAU - Williamson, Cynthia M AU - Williamson CM AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Pitel, Beth A AU - Pitel BA AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Golden, Crystal L AU - Golden CL AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Xu, Xinjie AU - Xu X AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. AD - Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Greipp, Patricia T AU - Greipp PT AUID- ORCID: 0000-0002-5536-9011 AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. AD - Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Ketterling, Rhett P AU - Ketterling RP AUID- ORCID: 0000-0001-6479-7897 AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. AD - Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Hoppman, Nicole L AU - Hoppman NL AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Peterson, Jess F AU - Peterson JF AUID- ORCID: 0000-0003-2496-8000 AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. AD - Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Harrison, Christine J AU - Harrison CJ AUID- ORCID: 0000-0002-0526-6794 AD - Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle-upon-Tyne, UK. FAU - Akkari, Yassmine M N AU - Akkari YMN AD - Cytogenetics and Molecular Pathology, Legacy Health, Portland, Oregon, USA. FAU - Tsuchiya, Karen D AU - Tsuchiya KD AUID- ORCID: 0000-0003-1406-5000 AD - Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. FAU - Shago, Mary AU - Shago M AD - Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. FAU - Baughn, Linda B AU - Baughn LB AUID- ORCID: 0000-0001-5229-4897 AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. LA - eng GR - U10 CA180899/CA/NCI NIH HHS/United States GR - U10 CA180886/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220719 PL - United States TA - Genes Chromosomes Cancer JT - Genes, chromosomes & cancer JID - 9007329 RN - 0 (Core Binding Factor Alpha 2 Subunit) SB - IM MH - Chromosome Aberrations MH - *Core Binding Factor Alpha 2 Subunit/genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics MH - Retrospective Studies PMC - PMC9549522 MID - NIHMS1838651 OTO - NOTNLM OT - B-ALL OT - FISH OT - RUNX1 OT - iAMP21-ALL OT - cytogenetics EDAT- 2022/07/01 06:00 MHDA- 2022/10/12 06:00 PMCR- 2022/12/28 CRDT- 2022/06/30 13:03 PHST- 2022/06/06 00:00 [revised] PHST- 2022/04/04 00:00 [received] PHST- 2022/06/27 00:00 [accepted] PHST- 2022/07/01 06:00 [pubmed] PHST- 2022/10/12 06:00 [medline] PHST- 2022/06/30 13:03 [entrez] PHST- 2022/12/28 00:00 [pmc-release] AID - GCC23084 [pii] AID - 10.1002/gcc.23084 [doi] PST - ppublish SO - Genes Chromosomes Cancer. 2022 Dec;61(12):710-719. doi: 10.1002/gcc.23084. Epub 2022 Jul 19.